A Zebrafish Mutant in the Extracellular Matrix Protein Gene efemp1 as a Model for Spinal Osteoarthritis

Osteoarthritis is a degenerative articular disease affecting mainly aging animals and people. The extracellular matrix protein Efemp1 was previously shown to have higher turn-over and increased secretion in the blood serum, urine, and subchondral bone of knee joints in osteoarthritic patients. Here,...

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Bibliographic Details
Published in:Animals (Basel) 2023-12, Vol.14 (1), p.74
Main Authors: Raman, Ratish, Bahri, Mohamed Ali, Degueldre, Christian, Caetano da Silva, Caroline, Sanchez, Christelle, Ostertag, Agnes, Collet, Corinne, Cohen-Solal, Martine, Plenevaux, Alain, Henrotin, Yves, Muller, Marc
Format: Article
Language:English
Subjects:
Arthritis
Biochemistry, biophysics & molecular biology
Biochimie, biophysique & biologie moléculaire
Cartilage
Connective tissue
CRISPR
ECM
efemp1
Embryos
Extracellular matrix
Genes
Genomes
Hernias
Life sciences
Macular degeneration
Mutation
notochord
Osteoarthritis
Proteins
Sciences du vivant
skeletal development
vertebra
Zebrafish
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Summary:Osteoarthritis is a degenerative articular disease affecting mainly aging animals and people. The extracellular matrix protein Efemp1 was previously shown to have higher turn-over and increased secretion in the blood serum, urine, and subchondral bone of knee joints in osteoarthritic patients. Here, we use the zebrafish as a model system to investigate the function of Efemp1 in vertebrate skeletal development and homeostasis. Using in situ hybridization, we show that the gene is expressed in the brain, the pharyngeal arches, and in the chordoblasts surrounding the notochord at 48 hours post-fertilization. We generated an mutant line, using the CRISPR/Cas9 method, that produces a severely truncated Efemp1 protein. These mutant larvae presented a medially narrower chondrocranium at 5 days, which normalized later at day 10. At age 1.5 years, µCT analysis revealed an increased tissue mineral density and thickness of the vertebral bodies, as well as a decreased distance between individual vertebrae and ruffled borders of the vertebral centra. This novel defect, which has, to our knowledge, never been described before, suggests that the mutant represents the first zebrafish model for spinal osteoarthritis.
ISSN:2076-2615
2076-2615
DOI:10.3390/ani14010074